Department of Gastroenterology, University Liver and Cancer Centre, Frankfurt University Clinic, Frankfurt am Main,
Department of Gastroenterology, University Liver and Cancer Centre, Frankfurt University Clinic, Frankfurt am Main, Germany.
Digestion. 2018;98(4):263-269. doi: 10.1159/000490888. Epub 2018 Aug 21.
Initially unresectable colorectal liver metastases can become resectable after chemotherapy. Combination chemotherapy with epidermal growth factor receptor (EGFR) antibodies has shown consistent high response rates in patients with all rat sarcoma (RAS) wild-type tumors.
Out of a cohort of 424 patients with metastatic colorectal cancer, we identified 30 patients with initially unresectable Kirsten RAS (KRAS) exon 2 wild-type colorectal liver metastases who received neoadjuvant chemotherapy with anti-EGFR agents between January 2008 and February 2014. In all patients, extended RAS analysis (KRAS and NRAS exon 3 codon 59/61 and exon 4 codon 117/146) was carried out retrospectively.
RAS mutation analysis identified further KRAS mutations in 4/30 patients (13.3%). In none of these 4 patients a R0 resection was achieved. In contrast, 15/26 (57.7%) RAS wild-type patients were R0 resected. Median overall survival was > 63.3 months in R0-resected patients versus 30.0 months in those with a R1 or R2 resection (HR 0.23; [95% CI 0.10-0.75; p = 0.008).
Our data suggest that a RAS wild-type and a R0 resection are the strongest predictors for overall survival.
最初不可切除的结直肠癌肝转移在化疗后可能变为可切除。表皮生长因子受体（EGFR）抗体联合化疗在所有野生型 RAS（RAS）肿瘤患者中显示出一致的高反应率。
在 424 例转移性结直肠癌患者的队列中，我们确定了 30 例最初不可切除的 Kirsten RAS（KRAS）外显子 2 野生型结直肠癌肝转移患者，这些患者在 2008 年 1 月至 2014 年 2 月期间接受了抗 EGFR 药物的新辅助化疗。所有患者均进行了扩展 RAS 分析（KRAS 和 NRAS 外显子 3 密码子 59/61 和外显子 4 密码子 117/146）。
RAS 突变分析在 4/30 例患者（13.3%）中发现了进一步的 KRAS 突变。在这 4 例患者中，均未达到 R0 切除。相比之下，26 例 RAS 野生型患者中有 15 例（57.7%）达到了 R0 切除。在达到 R0 切除的患者中，中位总生存期超过 63.3 个月，而在 R1 或 R2 切除的患者中为 30.0 个月（HR 0.23；95%CI 0.10-0.75；p=0.008）。
我们的数据表明，RAS 野生型和 R0 切除是总生存期的最强预测因素。
